What Makes Us Human

In a lab in Ireland, mice are drowning. Well, to be fair, it’s not so much that they’re drowning as that they are refusing to swim. The water is too big, their muscles are too small, and no one is coming to save them. Why even try?

So after four minutes of frantic paddling, they give up. They just lay there in their bowls of water, ocean-like to a mouse, and pant, exhausted.

But some of them don’t give up. This group of mice--the Rocky Balboas of the rodent world--keep swimming. They paddle on for six minutes and perhaps they would go longer, but the researchers pull them from the water.

The realists aren’t less healthy than their peers. They don’t have less strength of will, or character, or purpose. They aren’t whiners, they aren’t afraid of a little hard work, and they’re not unwilling to assume a stiff upper lip and carry on with the task at hand. (We presume. They’re mice; their interior lives remain a bit of a mystery.)

What we do know about them is that the bacteria found in their guts differ from that found in the Rockys’ guts. And as Michael Nute, Ph.D. student in Statistics at the University of Illinois at Urbana-Champaign, points out, this small fact may make a world of difference.

Gut instinct

Like all Illinois researchers, Nute (left) has lofty goals. “I want to cure autism,” he says, and then laughs at the enormity of the proposal.

But as grand as that goal may sound, it’s not out of reach. As in all things, Nute follows the research. A 2016 paper published in the journal Cell suggests that the secret to autism lies not in the brain but in the gut, or more explicitly, in the collection of microorganisms that live in the human gut and make life possible. “There are two huge nerves that run from the brain to the gut. For a while, we thought their communication was only one-way, from the brain to the gut. Now we know it’s bidirectional,” he says.

If we can identify gut bacteria and what it does, we should be on the right track.

But the first step in curing autism is not about tools or technology (though it relies upon them). The first step is recognizing that we’re not mice. And the second step is recognizing that, while we’re not mice, we might share some important similarities with them.

Nute explains that mouse models for autism, which are common, are promising. But there’s that first crucial problem again: we’re not mice. “The largest difference in microbiota is based on host species (chimps are different from mice, etc.), followed by diet. Right now, all we can really say is that Group A and Group B are different,” he says.

To get a full understanding of what things both differentiate and unite us, we need a full genetic tree.

The tree of life

There are the two philosophical questions that continue to guide and, at times, transform work like Nute’s: what is normal, and what makes us different from other species, and from one another?

Professor Tandy Warnow, in whose research group Nute works, is currently working on answering both questions by producing biological sequence analyses as it relates to genetic trees.

Genetic trees show relationships between organisms as they develop over time. For example, a researcher studying the relationships between humans and primates might sequence human DNA to find our closest primate relatives. Pinpointing these relationships--where organisms converge or diverge on the genetic tree--helps researchers construct an evolutionary narrative of life itself.

But sequencing is difficult. “When you sequence something, you get back a zillion short segments of DNA, or short strings of letters. You then have to put the pieces together, like doing a puzzle,” Nute explains.

In the case of bacteria, sequencing is like doing multiple puzzles at the same time with an almost infinite amount of very tiny pieces.

Warnow’s work is helping to fill out the genetic tree for bacteria. To do so, her team is currently using the SILVA database, which has over 500,000 bacterial sequences available. While researchers have assembled hundreds of thousands of these pieces, the puzzle they make isn’t anywhere complete.

Mapping the human microbiome is, after all, a relatively new endeavor. The Human Microbiome Project first appeared around 2007. As high-performance computing becomes more accessible to researchers, these data continue to become more plentiful.

Warnow and Nute use the Illinois Campus Cluster Program (ICCP) to study the human microbiome and add what they find to existing genetic trees. “I could run all of [my samples] on a desktop or laptop if I had many years and if I was sure the computer wasn’t going to melt,” Nute says.

Nute’s explanation of the research simultaneously projects the simplicity and complexity of the process, and why the Illinois Campus Cluster Program is so important.

“Take a sample, pull out bacteria, add chemicals, get DNA, magic happens. But to do this at that kind of scale--four billion DNA sequences against a genetic tree with 50,000 species on it--you need heavy duty computing. The ICCP is a version of heavy duty research-level computers, access to which we can’t find at Best Buy. Here, we can just log in and do our work.”

Nute’s research is still in the early stages, but advances in supercomputing resources are one of the elements that have pushed this kind of work forward in the past few years. “The overall effort is probably entering an adolescence of sorts, and the number of papers in the last two years on methods for processing metagenomics data (a particularly difficult type of microbiome sequencing data) has gone through the roof,” Nute explains.

As computing and analysis technologies advance, so will answers. Perhaps one day soon, we’ll understand just what makes us human.

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The Illinois Campus Cluster Program (ICCP) is the centralized hub of supercomputing resources at Illinois. Researchers from every field, as well as individuals, groups, and campus units, are welcome to invest in and use these resources. Researchers use the Campus Cluster for a variety of projects, including statistical modeling and data visualization. For more information, see https://campuscluster.illinois.edu/ or contact help@campuscluster.illinois.edu.